May. 21, 2014

Taking an engineer’s perspective to biology, Harvard genetics professor George Church has pioneered many of the technologies for sequencing and synthesizing—or, as he puts it, reading and writing—DNA, including the so-called “next-generation” techniques that have sped up and lowered the cost of sequencing. His work has spun off numerous biotech companies, and he is the director of—and first volunteer donor for—the Personal Genome Project, which aims to sequence and make public the genomes of 100,000 people in order to improve our understanding of human genetics, biology, and health. Also on Church’s to-do list? Contributing to President Obama’s BRAIN Initiative and the not-so-small matter of bringing the woolly mammoth back from extinction.

Science Friday chatted with Church about genomes and privacy, why resurrecting extinct species could be a boon to ecosystems, and the time he survived on an entirely synthetic diet.

The Personal Genome Project collects a ton of genetic data that requires analysis. How do you meet the challenge?

Our group, and many like ours, interprets many whole genome sequences every day. The main impediment to the research is not computing power, it's getting sharable genomic and medical information. Right now there're all these silos [in the genomic sequencing arena], and the number of silos is growing, so each silo has to have its own set of genomes in order to provide interpretation. If they don't share it, then the statistical power is low. We need a solution that allows us to share that genetic and trait data.

And the Personal Genome Project facilitates sharing. How did the idea for the nonprofit come about?

In 2005, we were developing technology as usual, minding our own business, and realized the technology was growing rapidly over a period of months, from bacterial genome sequencing toward bigger genomes. If we were going to do human, we were going to have to get permission. I looked at it and was surprised a little bit that under the status quo, researchers were promising anonymity to their subjects. It seemed that both the genome sequences and the traits were highly personally identifying, and the data were also easy to escape. I said, let's explore an alternative to disingenuously promising that we can keep genetic information from being re-identified, and instead recruit a cohort that specifically understands what it's getting into. That was the first radical thought in the Personal Genome Project. Bioethicists like it because we're being frank with the research subjects, and the researchers like it because they can share the data.

You really want a big data set about each person rather than have a data set that's very shallow, with just a few things about each person. We found, to our pleasant surprise, there were always more volunteers than needed. Now the Personal Genome Project has gone international. I guess you could call it spreading virally, in a good sense.

Whole genome sequencing can be used in personalized medicine, which involves tailoring treatments to individuals based on their genetic makeup. While the idea of personalized medicine has been around for a while, a lot of people say that it hasn't fully come to fruition. How do you respond to criticism that it should have happened already?

Some people get very rigid ideas of what they expect the future to be. In my opinion, it's already happened. Personalized medicine basically means molecular biology, and we've had that for a while. There're these ideas of pharmacogenomics [using genetic information to prescribe the most effective drugs with the least side effects] as the ‘killer app,’ and I think the ‘killer app’ is actually carrier testing [testing to see if someone carries a gene for a disease that could be passed on to his or her child]. Carrier testing we've had since 1991, with Myriad's [the molecular diagnostic company] now famous patent [of the breast cancer susceptibility genes, BRCA1 and 2]—but it's now hundreds of genes we’re testing. I really don't know anyone on the planet who's planning to reproduce who couldn't potentially benefit from carrier testing today. We don't have to wait another decade for personalized medicine. You've got goods and services available—they're just not being advertised properly, which is good, because the usual critique is that we've got a field full of hype. Well, this is the anti-hype, because personalized, preventive medicine [in the form of carrier testing] actually works, but not enough people know about it.

Your work extends beyond human genomes—you’re now a scientific advisor to a de-extinction project that plans to resurrect passenger pigeons and woolly mammoths. How did you get involved?

I had known about the passenger pigeon, but had not really obsessed about it the way Ben Novak [the research consultant involved with the bird’s revival], one of the students who spent a summer in my lab, did. But when we got on the subject, it suddenly clicked. Already, ancient DNA sequencing was becoming widespread. The next step was seeing if we understood what the ancient DNA was telling us by inserting pieces of it in existing genomes. That kind of combined my interests and others’ in ancient DNA with synthetic biology.

Why resurrect species like the woolly mammoth and passenger pigeon?

I think this is about keystone species and ecosystems. Some people think we should only focus on the living ones. But one way of focusing on the living ones is providing keystone species that help the ones that are still alive to survive better. [A keystone species is an organism that plays a disproportionally large role in its particular ecosystem.] The mammoth and the passenger pigeons are probably the most quintessential keystone species ever. The mammoth was certainly the largest on the tundra. The passenger pigeons were the largest flock of birds ever—almost five billion birds. They ate the seeds from chestnuts and beech and other trees. When they disappeared, these huge amounts of food that would fall from the trees onto the ground then caused a huge population explosion in rodents. That caused the population explosion in the ticks. It’s likely, but not proven, that that then caused an explosion in Lyme disease. The goal is helping ecosystems that help humans.

There's also the goal of awe-inspiring events, like Armstrong standing on the moon—of knowing that our environmental efforts are not doomed, where one by one the species die and they never come back. We know this is something that we can win. Then it becomes a matter of priorities, rather than a matter of impossibilities.

Do you have a scientific idol?

Growing up, Luther Burbank, I really liked. I tried to repeat some of his experiments as a kid, grafting and so forth. He was a botanist. He studied a lot of fruiting trees, like apples and pears, and he explored how you could graft one tree onto another. So you could take advantage of a tree that had resistance to infection in the roots, but then a different tree would have good fruit. I may be distorting this because most of my idolizing of Luther Burbank was when I was a kid—this is all remembrance of a nine-year-old, probably reading popular science books. George Washington Carver, I didn't know much about him, but I liked the idea that he would make many different uses of peanuts. As I grew older I started to like Barbara McClintock and Fred Sanger and Ed Lewis, all of whom had very, very tiny labs—which, obviously, I didn't emulate, but I thought it was really impressive how much they could do, just really by their thoughtfulness.

You seem to have been attracted to plants early on. Why is that?

I didn't want to hurt animals with experiments, whereas with plants, I didn't mind grafting a branch. I just thought it was the biggest thrill when I could graft the branch from one place to another, and a few months later it was perfectly fine, with a little scar tissue there. I also had two greenhouses full of orchids. My mother was a lawyer, and one of her clients couldn't pay her, so he paid her in orchids. I learned a lot about orchids.

Now you’re a vegan. How did that start?

I was in a quantum physics study one summer at MIT, and I had some spare time and joined a diet study. It was not only vegan, it was completely synthetic. Their goal was to deprive me of leucine and see what happened. Of course, depriving you of an essential amino acid like leucine is usually not a good thing. It can cause brain damage if done in excess. So, probably it did, and I could have, perhaps, been more successful if I hadn't been on this diet study. But in any case, I got inspired by it and learned a lot of nutrition that summer.

Veganism is a little difficult to maintain when you travel, but the fact is with my metabolism, I don't really need to eat more than once every couple of days anyway. Sometimes I'll miss all the meals in a day. I just forget about it, especially if my family is not around. I get focused on one particular topic that I obsess about, and if there's nothing that will interrupt me. I just keep going.

How do you come up with your ideas?

We have an unusual laboratory [at Harvard] that’s very interdisciplinary, with a bunch of new things that we’re working on that no one is working on anywhere else in the world. It’s easy to think of new things, because we're juggling a bunch of balls already, and so they collide in interesting ways. Because we solve problems, people come to us with interesting problems where they've done a lot of the work—they framed what's important—and we just have to figure out whether it's actually low hanging fruit or not, in terms of technology.

How often does an idea take off?

I think it's pretty rare that they never go anywhere. It's just a matter of time. Sometimes they are ahead of their time. Some people say being ahead of your time is really cool, but it's actually not cool. It's frustrating. What you need to do is to know how long to leave it on the shelf—to have the prepared mind, where the idea is ready to jump once the missing piece of the puzzle comes into being.